Maturational modification of hypoxic relaxation in ovine carotid and cerebral arteries: role of endothelium.

In light of evidence that hypoxia inhibits cerebrovascular calcium influx and that the contractile importance of calcium influx is greater in neonatal than adult cerebral arteries, the present studies evaluate the hypothesis that the mechanisms involved in hypoxic cerebral vasodilation are different in newborn and adult cerebral arteries. Intact segments of ovine common carotid (COM) and middle cerebral (MCA) arteries from 3- to 7-day-old newborn lambs and nonpregnant adults were mounted in tissue baths, contracted with 1 microM 5-HT, and exposed to hypoxia for 20 min (PO2 approximately 12 Torr). In endothelium-intact arteries, the magnitude of relaxation was similar and near maximal in all groups (range 82-92%) and did not vary with either age or artery type. However, the magnitude of hypoxic relaxation after endothelium removal was attenuated more in adult (COM 37 +/- 6%, MCA 53 +/- 7%) than in newborn (COM 75 +/- 5%, MCA 93 +/- 1%) arteries. In addition, endothelium-dependent responses to A23187, which like hypoxia increases endothelial cell concentrations of calcium, were attenuated in immature compared to mature arteries. Reductions of extracellular calcium concentration from 1.6 to 0.8 mM eliminated all age-dependent differences in relaxation responses to hypoxia. Together these data demonstrate that in newborn arteries, the endothelium-dependent component of hypoxic vasodilation is minimal, especially in intracerebral arteries, and robust relaxant responses to hypoxia depend on the high sensitivity of immature smooth muscle cells to decreases in PO2. In contrast, in adult arteries the smooth muscle sensitivity to decreases in PO2 is minimal and the endothelial component of hypoxic relaxation is particularly important in responses to hypoxia.